Zeng Jiafa, Usemann Jakob, Singh Kapil Dev, Jochmann Anja, Trachsel Daniel, Frey Urs, Sinues Pablo
Department of Biomedical Engineering, University of Basel, 4123 Allschwil, Switzerland.
University Children's Hospital Basel UKBB, University of Basel, 4056 Basel, Switzerland.
iScience. 2024 Nov 20;27(12):111446. doi: 10.1016/j.isci.2024.111446. eCollection 2024 Dec 20.
Asthma is a widespread respiratory disease affecting millions of children. Salbutamol is a well-established bronchodilator available to treat asthma. However, response to bronchodilators is very heterogeneous, particularly in children. Pharmacometabolomics via exhaled breath analysis holds promise for patient stratification. Here, we integrate a real-time breath analysis platform in the workflow of an outpatient clinic to provide a detailed metabolic snapshot of patients with asthma undergoing standard clinical evaluations. We observed significant metabolic changes associated with salbutamol inhalation within ∼1 h. Our data supports the hypothesis that sphingolipid metabolism and arginine biosynthesis mediate the bronchodilator effect of salbutamol. Clustering analysis of 30 metabolites associated with these pathways revealed characteristic metabotypes related to clinical phenotypes of poor bronchodilator responsiveness. We propose that such a metabolic fingerprinting approach may be of utility in clinical practice to quantify response to inhaled medications or asthma outcomes.
哮喘是一种影响数百万儿童的广泛存在的呼吸道疾病。沙丁胺醇是一种成熟的可用于治疗哮喘的支气管扩张剂。然而，对支气管扩张剂的反应非常不均一，尤其是在儿童中。通过呼出气分析进行的药物代谢组学有望实现患者分层。在此，我们将一个实时呼吸分析平台整合到门诊诊所的工作流程中，以提供正在接受标准临床评估的哮喘患者的详细代谢概况。我们观察到在吸入沙丁胺醇后约1小时内出现了显著的代谢变化。我们的数据支持这样的假设，即鞘脂代谢和精氨酸生物合成介导了沙丁胺醇的支气管扩张作用。对与这些途径相关的30种代谢物进行聚类分析，揭示了与支气管扩张剂反应性差的临床表型相关的特征性代谢型。我们提出，这种代谢指纹分析方法可能在临床实践中有助于量化对吸入药物的反应或哮喘的治疗结果。
